Browsing by Author "Lebovitz, Yeonwoo"
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- Emerging Developments in Microbiome and Microglia Research: Implications for Neurodevelopmental DisordersLebovitz, Yeonwoo; Ringel-Scaia, Veronica M.; Allen, Irving C.; Theus, Michelle H. (Frontiers, 2018-09-03)From immunology to neuroscience, interactions between the microbiome and host are increasingly appreciated as potent drivers of health and disease. Epidemiological studies previously identified compelling correlations between perinatalmicrobiome insults and neurobehavioral outcomes, the mechanistic details of which are just beginning to take shape thanks to germ-free and antibiotics-based animal models. This review summarizes parallel developments from clinical and preclinical research that suggest neuroactive roles for gut bacteria and their metabolites. We also examine the nascent field of microbiome-microglia crosstalk research, which includes pharmacological and genetic strategies to inform functional capabilities of microglia in response to microbial programming. Finally, we address an emerging hypothesis behind neurodevelopmental disorders, which implicates microbiome dysbiosis in the atypical programming of neuroimmune cells, namely microglia.
- Modulation of Neurodevelopmental Outcomes using Lactobacillus in a Model of Maternal Microbiome DysbiosisLebovitz, Yeonwoo (Virginia Tech, 2019-10-02)Neurodevelopmental disorders, such as autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder, are a heterogeneous set of developmental disorders affecting the central nervous system. Studies into their etiology remain challenging, as neurodevelopmental disorders frequently present with a wide range of biological, behavioral, and comorbid symptomologies. Increasing epidemiological reports of antibiotic use during pregnancy as a significant correlate of subsequent mental disorder diagnosis in children suggest a mechanism of influence via the maternal gut-fetal brain axis. Importantly, antibiotics cause dysbiosis of the gut microbiome and disrupt the delicate composition of the microbial inoculum transferred from mother to child, which is critical for development of the immune system and holds implications for long-term health outcomes. The research objective of this dissertation is to reveal a causal mechanism of maternal microbial influence on neurodevelopment by examining the brain's resident immune cells, microglia, and corresponding behavioral outcomes in a mouse model of antibiotics-driven maternal microbiome dysbiosis (MMD). We identify early gross motor deficits and social behavior impairments in offspring born to MMD dams, which paralleled hyperactivated microglia in brain regions specific to cognition and social reward. The MMD microglia also exhibited altered transcriptomic signatures reflective of premature cellular senescence that support evidence of impaired synaptic modeling found in MMD brains. We report that these deficits are rescued in the absence of Cx3cr1, a chemokine receptor expressed ubiquitously on microglia, to highlight a pathway in which maternal microbiota may signal to neonatal microglia to undergo appropriate neurodevelopmental actions. Finally, we characterize Lactobacillus murinus HU-1, a novel strain of an important gut bacterium found in native rodent microbiota, and demonstrate its use as a probiotic to restore microglial and behavioral dysfunction in MMD offspring.
- Molecular Phenotyping and Genomic Characterization of a Novel Neuroactive Bacterium Strain, Lactobacillus murinus HU-1Lebovitz, Yeonwoo; Theus, Michelle H. (2019-10-04)